We report a study of the role of hemodynamic shear stress in the remodeling and failure of a peripheral artery bypass graft. Three separate scans of a femoral to popliteal above-knee bypass graft were taken over the course of a 16 month period following a revision of the graft. The morphology of the lumen is reconstructed from data obtained by a custom 3D ultrasound system. Numerical simulations are performed with the patient-specific geometries and physiologically realistic flow rates. The ultrasound reconstructions reveal two significant areas of remodeling: a stenosis with over 85% reduction in area, which ultimately caused graft failure, and a poststenotic dilatation or widening of the lumen. Likewise, the simulations reveal a complicated hemodynamic environment within the graft. Preliminary comparisons with in vivo velocimetry also showed qualitative agreement with the flow dynamics observed in the simulations. Two distinct flow features are discerned and are hypothesized to directly initiate the observed in vivo remodeling. First, a flow separation occurs at the stenosis. A low shear recirculation region subsequently develops distal to the stenosis. The low shear region is thought to be conducive to smooth muscle cell proliferation and intimal growth. A poststenotic jet issues from the stenosis and subsequently impinges onto the lumen wall. The lumen dilation is thought to be a direct result of the high shear stress and high frequency pressure fluctuations associated with the jet impingement.